The central amygdala circuits in motivated behaviors Project Summary The central amygdala (CeA) contains heterogeneous cell types, with somatostatin-expressing (SOM+) neurons and protein kinase C-?-expressing (PKC-?+) neurons being two largest and largely non-overlapping populations. Previous studies have mainly focused on the roles of these neurons in fear conditioning, revealing that SOM+ and PKC-?+ CeA neurons differentially contribute to fear learning and expression. However, it is long recognized that the CeA contributes not only to behaviors driven by aversive stimuli, but also to those driven by appetitive stimuli, and to the generation of anxiety state. Indeed, recent studies show that distinct types of CeA neurons, such as SOM+ neurons, can drive appetitive behaviors and heightened anxiety. However, how the SOM+ as well as PKC-?+ CeA neurons participate in divergent motivational behaviors remains poorly understood. Bridging this knowledge gap will have important clinical implications for improved treatments, as CeA dysfunctions have been implicated in mood- or motivation-related disorders, including anxiety disorders, depression and drug addiction. We will address this question by investigating the in vivo response properties of SOM+ neurons and PKC-?+ neurons in the CeA during behaviors driven by either reward or punishment, and determining how these responses are used to control the functions of downstream circuits and, hence, behavior. Our central hypothesis is that CeA neurons influence learning or expression of reward seeking and punishment avoidance through their long-range projections to different targets. Based on our preliminary results, we devised an integrated approach, combining in vivo imaging, fiber photometry, optogenetics, chemogenetics and novel behavioral techniques, to test our hypotheses in the following Specific Aims: Aim 1. To determine the roles of SOM+ CeA neurons in motivational behaviors. Aim 2. To determine the roles of PKC-?+ CeA neurons in motivational behaviors. Aim 3. To determine how a CeA-BNST circuit contributes to anxiety-related behaviors.